To clarify the mechanisms of colon malignancy, each genetic event lying behind the progression of a colon tumor must be identified. Analysis of chromosome abnormalities, oncogene expression and the structural alteration, or linkage analysis of hereditary colon cancer, have provided some important clues to the molecular etiology of colon malignancy. A colon tumor-enriched cDNA library in which cDNAs expressed in normal colon tissue are subtracted has been constructed. The library has been screened and a unique cDNA clone, called cori-1, was isolated. Cori-1 is highly expressed in colon tumors. It is expressed in tumor cells, regardless of whether they are proliferating or density arrested. Sequencing analysis revealed the small gene (0.3 kb) had no identical sequence in the database. However, it does have an extensive homology with the antisense strand of the 5' untranslated region of the human krev-1 anti-oncogene, suggesting that unique transcripts may hybridize with krev-1 mRNA in the tumor cells and reduce the expression post-transcriptionally. It has been shown that biochemical and morphological differentiation can be induced in HT29 colon carcinoma cells by many types of agents. These systems are invaluable to the study of intestinal cell differentiation, as well as tumor etiology. However, the mechanism underlying these phenotypical changes still remain to be proved. We have generated differentiated subclones from sodium butyrate-treated HT29 cells. Cytogenetic analysis of two low tumorigenic subclones (CIII and CVII), as well as parental HT29 cells, showed chromosome numbers in the triploid range. However, modal chromosome numbers were concomitantly reduced with the loss of tumorigenicity. Notably, common chromosomes 10, 14q and 16q were missing in both of the subclones. These results suggest that the deficiency of factors located on the missing chromosomes triggers enterocyte differentiation and induces low tumorigenic phenotypes in the HT29 subclones.